Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer

Abstract

The clinical impact of circulating tumor cell (CTC) detection is controversial, mainly due to drawbacks of molecular approaches applied to this field. We sought to determine if the specific identification and counting of circulating tumor cells by cytomorphologic analysis has clinical usefulness. Peripheral blood (6 mL), treated using isolation by size of epithelial tumor cells, was obtained from 44 patients with primary liver cancer (PLC) and without metastases, 30 patients with chronic active hepatitis, 39 with liver cirrhosis, and 38 healthy individuals, and followed up for a mean period of 1 year. We searched for ␤-catenin mutations in 60 single microdissected CTCs. One patient with liver cancer developed extrahepatic metastases during follow-up. CTCs and microemboli were found in 23 of the 44 patients with liver cancer and in none of the patients with chronic active hepatitis, patients with cirrhosis, or healthy subjects. Their presence was significantly associated with tumor diffusion (P ‫؍‬ .0001) and portal tumor thrombosis (P ‫؍‬ .006). Both the presence (P ‫؍‬ .01) and number (P ‫؍‬ .02) of CTCs and microemboli were significantly associated with a shorter survival. ␤-Catenin mutations were found in 3 of 60 CTCs, arguing against their impact on the initial step of tumor cell invasion. In conclusion, the highly sensitive and specific detection of CTCs and microemboli may have clinical implications for cancer staging and outcome prediction. We also show the feasibility of molecular studies of individual circulating tumor cells, aimed at identifying gene mutations involved in tumor invasion. (HEPATOLOGY 2004;39:792-797.)

Enumeration, characterization, and collection of intact circulating tumor cells by cross contamination‐free flow cytometry

“…However, recent reports suggest that detection of CTM, which MCF-7 aggregates may mimic, is important because metastasis are being emphasized via CTM, rather than via a single CTC. Thus, a CTC at the center of a microembolus may play a metastatic role (2,31). According to this idea, the outer cells may undergo Figure 6.…”

Introducing, OncoTarget

“…In this study, we further optimized the size-based microfluidic chip that had previously reported by our group [16]. The principle behind this microfluidic device is that most cancer cells are larger size and less deformability than blood cells make them less likely to traverse through the channels while most blood cells pass through [23]. The size-based microfluidic device presented here thus encompasses major advances over the previous methods.…”

Enrichment of circulating tumor cells from a large blood volume using leukapheresis and elutriation: Proof of concept

“…In this study, a three-step sequential process was developed in an attempt to enrich and isolate CTCs from a large blood volume based upon their physical characteristics by (1) leukapheresis and (2) elutriation, and immunologically by (3) FACS. Current enrichment techniques are restricted by the low amount of blood that can be processed requiring sensitive detection methods to identify only a few CTCs within a large background of leukocytes (12,18,(42)(43)(44)(45). The use of leukapheresis to collect CTCs from cancer patients has the propensity to limit CTC escape and increase the amount of CTCs isolated by subsequent methods.…”

“…CTCs have generally been enriched based upon their physical character by their density using gradient centrifugation (9,14,15) and by their large size using micro-filtration (16)(17)(18)(19), or immunologically using antibodies targeting such as the epithelial cell adhesion molecule (EpCAM) that are immobilized on substrates including microfluidic chambers and magnetic beads for CTC adsorption (10,12,20). The enrichment of CTCs using gradient centrifugation and/ or immunomagnetic bead adsorption revealed a CTC incidence rate of 20% in ovarian cancer patients at primary diagnosis.…”